Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions diagnosed in the first 2-4 years of life which includes deficits in social interaction and communication. Although many brain regions are likely involved in ASD, the amygdala has been an area of great interest due to its role in emotional behavior and its numerous connections to other brain regions also implicated in ASD. Abnormal amygdala function has been demonstrated in ASD subjects and initial studies have identified altered amygdala neuroanatomy in post- mortem tissue from ASD adults. In addition, several magnetic resonance imaging (MRI) studies demonstrate that the amygdala is enlarged in young ASD subjects and that this enlargement occurs early in life. Recent reports not only confirm this enlargement but have also identified multiple patterns of amygdala growth in the first few years of life in children with ASD. These results suggest that the amygdala may be at the center of an abnormal brain network in ASD, and that amygdala pathology may vary across different groups in ASD. These findings also raise the possibility that the pattern of connectivity between the amygdala and other brain regions is altered in ASD. However, potential alterations in the white-matter pathways associated with the amygdala have not been thoroughly investigated. Diffusion tensor imaging (DTI) allows for in vivo visualization and investigation of pathways in the brain. DTI studies have already begun to identify white-matter abnormalities in the adult ASD brain, but no studies have investigated amygdala connectivity early in life when ASD symptoms first emerge and when abnormal amygdala enlargement is most pronounced. The proposed research will utilize DTI to investigate amygdala connectivity in a large longitudinal group of preschool-aged children with ASD and typically developing control children. By examining the integrity of connections to and from the amygdala in young children over several years, the proposed research will contribute significantly to our understanding of amygdala abnormalities in ASD. In addition, by examining white-matter pathways in a large group of extensively phenotyped children with ASD, this proposal seeks to further identify specific subtypes of neuropathology in ASD. PUBLIC HEALTH RELEVANCE: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that occurs in 1 in 88 children. Understanding the problems in brain structure and function is a critical first step towards developing treatments for the disorde. This project will utilize magnetic resonance imaging to search for altered brain connectivity in 3-4 year old children with ASD.